We show that busulfan-conditioned human IL-6–transgenic (hIL-6–transgenic) NSG (NSG+hIL6) mice reliably support the engraftment of malignant and premalignant human plasma cells, including from patients diagnosed with monoclonal gammopathy of undetermined significance, pre- and postrelapse myeloma, plasma cell leukemia, and amyloid light chain amyloidosis. This evidence concerns the gene IL6 and monoclonal gammopathy.